Type 2 Diabetes Treatment Intensification 2 Flashcards
Change in Blood Glucose as a Primary Marker
Not a suitable measurement as a surrogate outcome
- Can not be use as the only marker of success
FDA Guidance for Evaluating Drugs used to treat Type 2 Diabetes
Have to prove that the therapy is no worse at increasing risks of adverse effects (myocardial infarction)
Approvable
- Superiority
- No need for postmarketing study
Falls to the left of hazard ratio (less than 1)
Does not cross over Non Inferiority Boundaries:
- HR 1.3
- HR 1.8
Approvable
- Non-Inferiority
- No need for postmarketing study
Crosses hazard ratio (equal or greater than 1)
Does not cross over Non Inferiority Boundaries:
- HR 1.3
- HR 1.8
Approvable
- Non-Inferiority
- Need for postmarketing study
Crosses hazard ratio (equal or greater than 1)
Crosses Non Inferiority Boundary
- HR 1.3
Does not cross Non Inferiority Boundary
- HR 1.8
Not Approvable
- Inferior
Does not cross hazard ratio (Greater than 1)
Crosses Non Inferiority Boundary
- HR 1.3
- HR 1.8
Not Approvable
- Underpowered
Crosses hazard ratio (equal or greater than 1)
Crosses Non Inferiority Boundary
- HR 1.3
- HR 1.8
Common CVOT Features
Inclusion Criteria identifies people at high risk of CV Outcomes
- CV Risk Factors
- Prior CV Events
Placebo Controlled Trial
Patient on Glucose Lowering Therapy according to guidelines
Primary Outcome: Major Adverse CV Events
Non-Inferiority Design
Primary Outcomes of CVOT
Major Adverse Cardiovascular Events
- Nonfatal Myocardial Infarction
- Nonfatal Stroke
- Cardiovascular Related Death
- Hospitalization for Unstable Angina
- Hospitalization for Heart Failure
Issues with CVOT
- Evidence is Hard to apply and generalize
- Unknown effects on microvascular
- Relative benefits of antihyperglycemic agents is unknown (Except: Glimepiride and Linagliptin)
- CV safety was not a major concern
Slide 18
What medication causes increased risk of amputation?
Canagliflozin
DPP4i
- Safety Signal
Pancreatitis
GLP1ra
- Safety Signal
Retinopathy
Gastroparesis
Suicide Risk
SGLT2i
- Safety Signal
Genitourinary Infection
Diabetic Ketoacidosis
Fracture
Thiazolidinediones
- Safety Signal
Heart Failure
Macular Edema
Distal Fractures (Women)
Sulfonyulureas
- Safety Signal
Increased risk of Cardiovascular Events
- Do not use Glyburide
- If you have to use Gliclazide
Diabetes Canada Guidelines
- Patient not reaching targets on noninsulin existing antihyperglycemic agent
Add a basal insulin regimen
- Decreased risk of hypoglycemia
- Decreased risk of weight gain
Basal is better than:
- Pre-mixed
- Bolus regimen
Diabetes Canada Guidelines
- Patient is on basal insulin regimen and main priority is lowering risk of hypoglycemia. Which insulin should be used?
a) Glargine U-100/U-300, Detemir, Degludec > NPH
- Reduces risk of nocturnal and symptomatic hypoglycemia
b) Degludec or Glargine U-300 > Glargine U-100
- Reduces overall and nocturnal hypoglycemia
- Reduces risk of severe hypoglycemia in patients at high CV risk
Diabetes Canada Guidelines
- Patient is on insulin and still not meeting targets
Adjust dose OR Add an additional antihyperglycemic agent
- DPP4i
- GLP1ra
- SGLT2i
These choices avoid weight gain and reduce risk of hypoglycemia
Diabetes Canada Guidelines
- When adding a bolus insulin to additional antihyperglycemic agents
Rapid Acting (Aspart, Glulisine, Lispro) > Short Acting (Regular)
- Better glycemic control
Diabetes Canada Guidelines
- How should insulin be initiated
Bolus is initiated using a stepwise approach
- Start with 1 injection at meals with additional mealtime injections if necessary
–> To achieve A1c reduction while lowering the risk of hypoglycemia
Better than initiating patient at bolus injection at every meal
